Proliferation of bovine aortic smooth muscle cells (SMCs) induced by thrombin, basic fibroblast growth factor, or serum is inhibited by anionic, nonsulfated aromatic compounds that mimic many of the effects of heparin. Among these compounds are aurintricarboxylic acid (ATA) and a newly synthesized polymer of 4-hydroxyphenoxy acetic acid (compound RG-13577). Iodinated-or 14 C-labeled compound RG-13577 binds to cultured SMCs in a highly specific and saturable manner. Scatchard analysis of the binding data revealed the presence of an estimated lxlO 7 binding sites per cell with an apparent dissociation constant of 3xlO~6 mol/L. Binding of radiolabeled RG-13577 was efficiently competed for by related aromatic anionic compounds and by apolipoprotein E, but not by heparin, heparan sulfate, suramin, or various purified growth factors and extracellular matrix proteins.

The preparation, characterization and biological properties of some polyanionic polymers are reported. These polymers are constructed with repeating phenol-based monomers. The anionic groups attached to the aromatic nucleus provide the basis for binding to basic domains of proteins. Scaf-*Author to whom correspondence should be addressed.at CARLETON UNIV on June 21, 2015 jbc.sagepub.com Downloaded from 318 fold flexibility permits the polyanionic polymers to adopt low energy conformations suitable for interacting with coagulation proteins and an anti-DNA monoclonal antibody. Structure activity relationships (SAR) and comparisons with aurintricarboxylic acid are described. The polymers doubled the clotting time in the APTT assay with value ranging from 10-1000 μg/mL. Binding to an anti-DNA monoclonal antibody occurred with ICso values of 0.3-5.0 μg/mL. INTRODUCTIOÑ